The proposed program is a multidisciplinary investigation of the causes and treatment of mental retardation. Projects include basic and applied studies related to developmental neurochemistry, lysosomal hydrolases, chemical characterization of normal and pathological tissues, cultures of normal and neoplastic cells and clinical studies of inborn errors of metabolism. The developmental neurochemical studies will examine biosynthetic and regulatory aspects of the complex glycoconjugates of cell-surface membranes. New techniques for analysis of brain glycolipids at the molecular species level will be sought. The role of lipids, proteins, proteolipids and related enzymes in myelinogenesis will be examined. Normal and allotypic mutant lysosomal enzymes will be purified and studied in attempts to explain and ameliorate the pathological processes. Human skin fibroblasts and lymphocyte cultures from some thirty different genetic diseases are available for investigations of these disorders. Clinical investigations will focus primarily on metabolic studies of genetic diseases. Projects designed to elucidate the pathological processes involved and evaluate therapeutic regimens are proposed for phenylketonuria, Vitamin B6-Dependent Epilepsy and Steely-Hair Syndrome. Correlative studies of dental-neurological malformations are also planned. The use of animal models for evaluation of therapeutic transplantation is proposed. IDEN*